The objective of the present proposal is to ivestigate correlations between ionic fluxes mediated by the sodium pump on the one hand, and metabolic conditions prevailing inside the cell, on the other hand. A thorough quantitative analysis of these correlations is prerequisite to a complete kinetic formulation of the operation of the sodium pump, and will help throw light on the molecular mechanisms underlying both the observed ion fluxes and the accompanying biochemical transformations. The sodium pump of cell membranes is known to engage in Na:Na exchange (in addition to the normal Na:K exchange) whenever intracellular (ADP) is raised. The kinetics of this complex behavior will be investigated, mainly on the squid giant axon, by means of the internal dialysis technique, which allows (1) experimental control of the independent variables (i.e., electric, metabolic and ionic parameters) and (2) measurement of the following dependent variables: Na and K in- and effluxes, ATP hydrolysis, and ATP:ADP exchange. Using proper stability constants for magnesium-nucleotide complexes, as well as equilibrium constants for various nucleotide equilibria (myokinase, phosphagen kinase), internal perfusion media will be prepared whose composition with respect to ATP, ADP, AMP, their Mg complexes, free Mg2 ion levels, as well as pH, will be exactly known. Conditions will be chosen such that either the Na:K exchange mode or the Na:Na exchange mode predominate, and a detailed kinetic analysis will be made of either mode of operation with respect to the pertinent substrates and products (Nai; Ki; Nao; ko).